This program-project inquires into the basic mechanisms which regulate the replication and differentiation of normal and cancer cells. A combination of genetical, biochemical and cell biological approaches is used to address the following problems: 1. An elucidation of the mechanisms by which RNA polymerases bind to defined DNA templates and carry out a regulated transcription of specific genes. 2. The clarification of the role of gene structure and other gene products in the regulation of transcription. 3. A description of the molecular reactions by which primary gene transcripts are processed into functional messenger RNA species. 4. The identification of the components in nuclear envelopes and the definition of their roles in the regulation of nuclear function. 5. The identification of the active components of the DNA replicase system and a definition of the processes by which DNA-chromatin complexes are replicated. 6. The development of genetic systems in eucaryotes (i.e., Physarum polycephalum and mouse teratoma cells) for the study of the regulation of cell replication and differentiation.